To investigate the distribution and development of common allergens in children in Hangzhou area, and to provide an epidemiological basis for the prevention, diagnosis, and treatment of allergic diseases in this area. This study is a retrospective study, selecting 3 524 children who underwent allergen screening at DiAn Medical Laboratory Center (Hangzhou) Co., Ltd. from January 2022 to January 2024 as the research subjects, including 2 012 males and 1 512 females. Among them, there were 1 098 infants (0-1 year olds), 1 673 toddlers (1-3 year olds), and 753 children (3-14 year olds). Immunoblotting was used to detect 21 allergen-specific immunoglobulin E (sIgE) antibodies. The positive rates of various allergens were calculated according to gender, age, and other factors, and the epidemiological characteristics and trends were analyzed. The results showed that the overall positive rate of sIgE was 60.33% (2 126/3 524). The main inhaled allergens were Dermatophagoides pteronyssinus/Dermatophagoides farinae (992, 28.15%), dog dander (295, 8.37%) and cat dander (181, 5.13%). The main food allergens were milk (696, 19.75%), egg white (541, 15.36%) and shrimp (205, 5.83%). Boys had significantly higher sIgE positivity rates than girls for Dermatophagoides pteronyssinus/Dermatophagoides farinae(642, 31.90%, χ2=10.10, P=0.001), house dust(61, 3.02%, χ2=5.12, P=0.024), cat dander(124, 6.16%, χ2=4.06, P=0.044), mold combinations(103, 5.14%, χ2=7.51, P=0.006), and tree pollen combinations(42, 2.07%, χ2=5.44, P=0.020) (all P<0.05); With age, there was a significant increase in positivity rates for house dust mite/dust mite, house dust, mold combinations, milk, and beef (all P<0.05), and a significant decrease in positivity rates for cockroach consumption, egg whites, shrimp, crab, cod, lobster/scallop, and soybeans (all P<0.05), the positive rates of only ingestive allergens decreased significantly ( P<0.001), and the positive rates of only inhalant and mixed allergens increased significantly ( P<0.001). In conclusion,in the Hangzhou area, dust mites are the most common inhalant allergens among children with allergic diseases, while milk is the most common food allergen. Boys are more sensitive to inhalant allergens, and as children grow older, the positive rates for different allergens undergo significant changes. Dynamic monitoring of changes in specific IgE antibodies to various allergens can assist in the diagnosis, prevention, and treatment of allergic diseases.

Objective:To analyze the epidemiological characteristics of cases involving monkey injuries at medical institutions surrounding Qianlingshan Park in Guiyang City, and to provide a reference basis for preventive measures to reduce monkey injuries and standardized post-exposure treatment.Methods:A retrospective cross-sectional study was conducted, collecting 1 900 cases of monkey-induced injuries in Qianlingshan Park treated at the outpatient clinic of Guizhou Provincial Center for Disease Control and Prevention and the Department of Surgery at Qianling Hospital, Guiyang City, from 2021 to 2024. Statistical analysis was performed using Pearson′s chi-square test.Results:Total of 1 900 cases of monkey-related injuries in Qianlingshan Park were collected from 2021 to 2024. The exposure time distribution exhibited significant seasonality, with 48.58% of cases occurring during July and August, totaling 923 cases, indicating a peak in the summer. There were 774 male patients and 1 126 female patients, with a ratio of 1∶1.45.and significant differences were observed between different age groups and genders (χ2=195.00, P<0.001), with the highest number of cases occurring in the 0-9 and 20-29 age groups, accounting for 22.05%(419 cases) and 21.79%(414 cases), respectively. The upper limbs were the most common injury site, accounting for 50.84% of the total cases(966 cases in total), with significant differences between gender and injury location (χ2=22.00, P<0.001), Among females, the proportion of injuries to the upper and lower limbs (30.11% and 16.47%, respectively) was higher than that among males (20.74% and 8.63%, respectively). The majority of injuries were classified as Grade Ⅲ, making up 57.38% of cases(1 069 cases in total). Self-treatment after exposure was the most common approach(60.44%), with significant differences observed between wound severity and treatment method (χ2=6.90, P=0.032), Patients with Grade Ⅱ and Grade Ⅲ wounds were more likely to choose self-management (26.84% and 33.23%, respectively) than outpatient management (15.14% and 24.15%). Approximately 98.05% (1 863 cases) of monkey-injured patients had received rabies vaccinations. Conclusions:This study analyzes monkey-related injuries in Qianlingshan Park from 2021 to 2024, clarifying the temporal distribution of injuries, demographic characteristics, injury sites, and treatment methods. The findings provide references for optimizing human-monkey conflict management and the prevention and control of zoonotic diseases in urban ecological parks.

Objective:To analyze the epidemiological and clinical characteristics of respiratory pathogens in China.Methods:This study was a cross-sectional study, which encompassed 19 core units of the clinical pathogen network and established a three-tiered clinical pathogen surveillance system. Thirty respiratory samples were collected every two weeks from various units from January to December 2024, and the clinical and pathogen diagnostic information were gathered. A total of 11 864 samples were tested using this system. The tier-1 clinical pathogen surveillance system covered influenza A virus (Flu-A), influenza B virus (Flu-B), respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The tier-2 clinical pathogen surveillance system focused on 18 key respiratory pathogens. The tier-3 clinical pathogen surveillance system further clarified whether any emerging infectious diseases had occurred.Results:The tier-1 clinical pathogen surveillance system showed Flu-A predominated in December, Flu-B predominated in January, SARS-CoV-2 peaked in March and August, whereas RSV circulated sporadically throughout the year. Geographic trends were broadly consistent across the seven major regions, although Flu-A detection in December was notably higher in Northeast China (48.1%(111/231)) and East China (36.2%(148/409)), and RSV detection was concentrated in the Northwest and South China from January to March. Data from the tier-2 clinical pathogen surveillance system indicated that Streptococcus pneumoniae, Mycoplasma pneumoniae, rhinovirus, and adenovirus were detected year-round, of these, Streptococcus pneumoniae and rhinovirus showed elevated positive detection rates from August to September, while adenovirus peaked in January. Legionella pneumophila was not detected throughout the year, and other pathogens fluctuated throughout the year without a consistent pattern. The predominant etiologic agents of pediatric pneumonia were Mycoplasma pneumoniae (35.0%(105/300)), rhinovirus (25.7%(77/300)), and adenovirus (17.3%(52/300)), whereas adult pneumonia was mainly caused by Streptococcus pneumoniae (10.5%(29/277)), Staphylococcus aureus (6.9%(19/277)), Mycoplasma pneumoniae (6.9%(19/277)), and Flu-A (6.1%(17/277)). The tier-3 clinical pathogen surveillance system did not identify any emerging respiratory pathogens. Conclusion:Respiratory pathogens in China in 2024 exhibit distinct temporal and spatial distribution patterns and vary among different populations.

Objective:To analyze the gene mutations of 18 patients with plasminogen (PLG) deficiency and to explore the clinical manifestations caused by PLG gene mutations.Methods:This study belongs to observational study-descriptive study: case series.Clinical data from 18 patients with PLG deficiency admitted to the First Affiliated Hospital of Wenzhou Medical University from January 1st, 2021 to May 31st, 2025 were collected. The age ranged from 16 to 70 years old, with an average of 48 years old. Among them, there were 10 males and 8 females. Anticoagulant blood samples were taken before treatment to measure and analyze plasminogen activity (PLG:A), plasminogen antigen (PLG:Ag), protein C activity, protein S activity, fibrinogen, antithrombin activity, D-dimer, and fibrin (fibrinogen) degradation products. PCR direct sequencing was used to analyze the 19 exons and flanking sequences of the PLG gene in these patients, and reverse sequencing was employed to verify the suspected mutations.Results:For the 18 patients, cranial MRI showed fresh cerebral infarction lesions, and PLG:A levels ranged from 19% to 67%, while no other lab indicators showed significant abnormalities, all presenting with dysplasminogenemia. Genetic analysis revealed five types of PLG gene mutations: c.1858G>A (p.Ala620Thr) heterozygous mutation, c.1858G>A (p.Ala620Thr) homozygous mutation, c.398A>G (p.His133Arg) heterozygous mutation, c.2108G>A (p.Gly703Asp) heterozygous mutation, and c.1702G>A (p.Gly568Arg) heterozygous mutation. Among the above, the c.1858G>A heterozygous mutation was the most common, and c.398A>G and c.1702G>A were identified for the first time.Conclusion:Patients with plasminogen deficiency caused by PLG gene defects are prone to occur cerebral infarction events, which may be related to impaired fibrinolytic function due to PLG gene mutations.

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

OBJECTIVE: To investigate the molecular pathogenic mechanisms of a family with hereditary factor Ⅶ (FⅦ) deficiency. METHODS: A family (3 generations, 12 members) with hereditary FⅦ deficiency, in which the proband presented with menorrhagia and was admitted to the First Affiliated Hospital of Wenzhou Medical University in April 2023, was selected as the study subject. Clinical data of the family members were collected. Peripheral venous blood samples were collected from all 12 members for routine coagulation tests and genomic DNA extraction. All exons and flanking sequences of the F7 gene were amplified by PCR and analyzed by Sanger sequencing. Thrombin generation assay was performed to evaluate the coagulation potential of the proband and her parents. Multiple online bioinformatics software tools were used to analyze the conservation and pathogenicity of candidate variants identified in the proband. The pathogenicity of variant was classified according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). Homology modeling of the variant FⅦ protein was performed using homology modeling (SWISS-MODEL). Amino acid sequence alignment between wild-type and variant FⅦ proteins was conducted using MEGA v7, and spatial conformational differences were analyzed using PyMOL to assess the potential impact of the F7 gene variants on the structure and function of the FⅦ protein. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: Coagulation tests showed that the proband's prothrombin time (PT) was significantly prolonged to 33.1 s, and both factor Ⅶ activity (FⅦ:C) and antigen (FⅦ:Ag) levels were reduced to 2%. Her parents, eldest sister, second sister, younger brother, and four children all showed mildly prolonged PT, with FⅦ:C and FⅦ:Ag levels approximately 50% of normal. Genetic sequencing identified compound heterozygous variants in the F7 gene of the proband: a heterozygous missense variant c.722C>A (p.Thr241Asn) in exon 7, and a heterozygous deletion variant c.1261_1261delA (p.Ile421Ser*fs75) in exon 8. Retrieval from domestic and international databases found no previous reports of the latter variant, suggesting it is novel. Familial co-segregation analysis confirmed that these variants were inherited from her father and mother, respectively. The thrombin generation assay demonstrated that the proband had a significantly decreased peak thrombin height (peak ratio: 29.5%), significantly increased thrombin lag time ratio and time-to-peak ratio (3.03 and 2.93, respectively), but only a mildly decreased endogenous thrombin potential (ETP) ratio of 90.7%. Online bioinformatics analysis indicated that threonine-241 (p.Thr241) in the FⅦ protein was not conserved, while isoleucine-421 (p.Ile421) was highly conserved. Both the p.Thr241Asn and p.Ile421Serfs*75 variant sites in the proband's F7 gene were predicted to be pathogenic. According to the ACMG guidelines, the p.Thr241Asn (PM3+PP1+PP3+PP4+PP5) and p.Ile421Ser*fs75 (PM2+PM4 +PP1+PP3+PP4) variants were both classified as "likely pathogenic". Structural analysis of the FⅦ protein indicated that the p.Ile421Ser*fs75 frameshift variant led to the substitution of Cysteine-428 by Alanine, preventing the formation of a critical disulfide bond between amino acid residues 400 and 428 present in the wild-type FVII protein. CONCLUSION The compound heterozygous variants p.Thr241Asn and p.Ile421Ser*fs75 in the F7 gene are likely the genetic etiology responsible for the reduced FⅦ levels in this hereditary FⅦ deficiency family.
Adult ; Female ; Humans ; Male ; Middle Aged ; China ; Factor VII/chemistry* ; Factor VII Deficiency/genetics* ; Heterozygote ; Mutation ; Pedigree ; East Asian People/genetics*

OBJECTIVE: To analyze the phenotype and genotype of a family with hereditary coagulation factor Ⅹ (FⅩ) deficiency and preliminarily explore its molecular pathogenesis. METHODS: A hereditary FⅩ deficiency pedigree presented at the First Affiliated Hospital of Wenzhou Medical University on August 13, 2024 was selected as the study subject. Coagulation parameters of the proband and her family members (7 individuals from 3 generations) were measured using a one-stage clotting assay. All of the 8 exons and flanking sequences of the F10 gene were amplified by PCR and directly sequenced. Bioinformatics software was used to analyze the functional impact and pathogenicity of the variant proteins, as well as the spatial conformational changes and evolutionary conservation of the mutation sites. This study has been approved by the Medical Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband exhibited significantly abnormal prothrombin time (PT, 33.3 s), activated partial thromboplastin time (APTT, 47.7 s), and FⅩ activity (FⅩ:C, 3%), while other coagulation parameters remained normal. The plasma thromboplastin generation test (PTGT) demonstrated that the proband and her children had lower thromboplastin generation levels compared with the healthy control group, and the proband's thromboplastin generation capacity was more severely impaired. Genetic analysis revealed that the proband, her daughter, and grandson have all harbored a heterozygous missense variant c.212T>C (p.Phe71Ser) in exon 2 of the F10 gene, which was located in the β-sheet core region of the Gla domain. The variant has altered surrounding hydrogen bonds and disrupted calcium-binding sites. Additionally, the proband, her son, and granddaughter have all carried a heterozygous missense variant c.1270G>T (p.Val424Phe) in exon 8, which increased the side-chain volume, leading to steric hindrance in the catalytic domain and impaired coagulation function. Bioinformatics analysis confirmed that both p.Phe71Ser and p.Val424Phe were pathogenic variants, with Phe71 and Val424 being highly conserved residues. CONCLUSION The reduced FⅩ levels in this hereditary FⅩ-deficient family may be attributed to the heterozygous missense variants c.212T>C (p.Phe71Ser) in the exon 2 and c.1270G>T (p.Val424Phe) in the exon 8 of the F10 gene.
Humans ; Female ; Male ; Pedigree ; Adult ; Heterozygote ; Mutation ; Middle Aged ; Factor X/genetics* ; Exons ; Factor X Deficiency/genetics*

OBJECTIVE: To investigate the molecular mechanism for a family with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: The proband, a 63-year-old female, was admitted to the First Affiliated Hospital of Wenzhou Medical University in August 2024 for lumbar disc herniation. Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), and FⅫ activity (FⅫ:C), were carried out for the proband and her family members (9 individuals from three generations) using a one-stage clotting assay. The level of FⅫ antigen (FⅫ:Ag) was determined with an Enzyme-linked immunosorbent assay (ELISA). Sanger sequencing was conducted to identify potential variants in the F12 gene. Multiple in silico tools were used to predict the conservation, hydrophobicity, and structural impact of the identified variants. Recombinant expression plasmids were constructed and transiently transfected into HEK293T cells. The recombinant FⅫ protein was analyzed using Western blotting (WB) and ELISA. This study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (Ethics No.: KY2022-R193). RESULTS: The proband showed a markedly prolonged APTT (160.3 s) and significantly decreased FⅫ:C (2%) and FⅫ:Ag (5%) levels. Analysis of the F12 gene sequence revealed a 46C/T genotype in the promoter region, a heterozygous c.1457G>A (p.Cys467Tyr) missense variant in exon 12, and a heterozygous c.1561G>A (p.Glu502Lys) missense variant in exon 13. Bioinformatic analysis showed that the p.Cys467 is highly conserved across various species, and the p.Cys467Tyr variant may affect local structural stability of the FⅫ protein. The p.Cys467Tyr variant had no effect on the transcription of the F12 gene. However, the variant has significantly decreased the FⅫ:Ag levels and FⅫ protein expression in the cell culture supernatant compared to the wild-type expression vector, while in the cell lysate, it is higher than the wild-type expression vector. In other words, the p.Cys467Tyr variant has probably caused a secretion defect of FⅫ protein. CONCLUSION The 46C/T genotype, the heterozygous p.Cys467Tyr missense variant, and the heterozygous p.Glu502Lys missense variant are associated with reduced plasma FⅫ levels in this pedigree. The p.Cys467Tyr variant, which was unreported previously, did not affect the synthesis of FⅫ but may have resulted in a secretion defect.
Humans ; Female ; Middle Aged ; Mutation, Missense ; Pedigree ; HEK293 Cells ; Male ; Factor XII/genetics* ; Adult ; Factor XII Deficiency/genetics*

Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.

Objective:To investigate the molecular pathogenic mechanism of venous thrombosis caused by heterozygous missense mutations in two protein C (PROC) genes through laboratory phenotype analysis, genetic mutation analysis, and in vitro expression experiments.Methods:Two probands presented with venous thromboembolism at the First Affiliated Hospital of Wenzhou Medical University. Clinical data and blood samples were collected from the probands and their family members to evaluate the plasma protein C (PC) activity (PC∶A), PC antigen (PC∶Ag) levels, and other relevant coagulation parameters. The anticoagulant capacity was assessed using the thrombin generation test (TGT). The mutation sites of the PROC gene were identified using direct DNA sequencing. Bioinformatics software was used to analyze the conservation and pathogenicity of the mutated gene. PyMOL software was used for the analysis of the protein three-dimensional models and interactions between mutated amino acids. Wild-type and two mutant expression vectors were constructed and HEK293T cells were transiently transfected. Total cellular RNA was extracted from positively transfected cells to investigate the transcriptional levels of the mutant PROC gene. Enzyme-linked immunosorbent assay, Western blot, and cellular immunofluorescence assays were used to investigate the translation levels of the mutant PROC protein.Results:Probands 1 and 2 exhibited PC∶A levels of 35% and 40% and PC∶Ag levels of 44% and 39%, with increasing D-dimer levels to 4.42 mg/L and 0.83 mg/L, respectively. Meanwhile, other coagulation parameters revealed no significant abnormalities. TGT demonstrated impaired anticoagulant function in both proband witnesses and their familial PC carriers. Sequencing analysis revealed heterozygous missense mutations c. 833T>C (p. Leu278Pro) in proband 1 and c. 1330T>C (p. Trp444Arg) in proband 2 within exon 9 of the PROC gene. Conservation analysis revealed that Leu278 and Trp444 were highly conserved across homologous species. Pathogenicity analysis indicated that both p. Leu278Pro and p. Trp444Arg mutations are deleterious. Protein modeling analysis demonstrated that both mutations induce structural alterations in the protein. In vitro expression experiments revealed that compared with the wild-type, both p. Leu278Pro and p. Trp444Arg mutations showed no significant differences in the mRNA expression level of the PC protein. However, both mutations caused significantly lower PC∶Ag content and protein expression levels in the cell culture supernatant compared with the wild-type, whereas higher levels were observed in the cell culture lysate. This indicates the association of both mutations with the secretion function of the PC protein.Conclusion:The heterozygous missense mutations p. Leu278Pro and p. Trp444Arg in exon 9 of the PROC gene in both probands are associated with decreased PC levels.